US 11,684,616 B2
Azalactam compounds as HPK1 inhibitors
Joyann Barber, San Diego, CA (US); Sujin Cho-Schultz, San Diego, CA (US); Matthew L. Del Bel, San Diego, CA (US); Rebecca Anne Gallego, San Diego, CA (US); Mingying He, San Diego, CA (US); Mehran Jalaie, San Diego, CA (US); Robert Steven Kania, Del Mar, CA (US); Michele Ann McTigue, Encinitas, CA (US); Sajiv Krishnan Nair, Vista, CA (US); Anne-Marie Dechert Schmitt, Westerly, RI (US); Jamison Bryce Tuttle, Marblehead, MA (US); Dahui Zhou, Groton, CT (US); and Ru Zhou, Carlsbad, CA (US)
Assigned to PFIZER INC., New York, NY (US)
Filed by PFIZER INC., New York, NY (US)
Filed on Apr. 30, 2021, as Appl. No. 17/246,551.
Claims priority of provisional application 63/018,689, filed on May 1, 2020.
Prior Publication US 2022/0401424 A1, Dec. 22, 2022
Int. Cl. C07D 471/04 (2006.01); C07D 519/00 (2006.01); A61K 31/444 (2006.01); A61K 45/06 (2006.01)
CPC A61K 31/444 (2013.01) [A61K 45/06 (2013.01); C07D 471/04 (2013.01); C07D 519/00 (2013.01)] 33 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 is (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, —N(R5)(R6), or (C3-C6)cycloalkyl, wherein said (C1-C6)alkyl, halo(C1-C6)alkyl, and (C3-C6)cycloalkyl are substituted with 0 or 1 substituent that is hydroxy, cyano, (C1-C6)alkyl, or (C1-C6)alkoxy, wherein:
R5 and R6 are each independently hydrogen or (C1-C6)alkyl that is substituted with 0, 1, or 2 substituents independently selected from the group consisting of halogen, (C1-C6)alkoxy, cyano, and hydroxy, or
R5 and R6 taken together with the nitrogen to which they are attached form a (4- to 8-membered)heterocycloalkyl that is substituted with 0, 1, or 2 substituents independently selected from the group consisting of halogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy;
R2 is N(R7)(R8), wherein:
R7 and R8 are each independently hydrogen or (C1-C6)alkyl that is substituted with 0, or 1 substituent that is halogen, (C1-C6)alkoxy, cyano, or hydroxy; or
R7 is hydrogen or (C1-C6)alkyl that is substituted with 0, or 1 substituent that is halogen, (C1-C6)alkoxy, cyano, or hydroxy; and R8 taken together with the nitrogen to which it is attached and taken together with R3a and the carbon to which it is attached form a (4- to 6-membered)heterocycloalkyl that is substituted with 0, 1, or 2 substituents independently selected from halogen, hydroxy, (C1-C3)alkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, and halo(C1-C6)alkoxy; or
R7 and R8 taken together with the nitrogen to which they are attached form a (4- to 6-membered)heterocycloalkyl that is substituted with 0, 1, or 2 substituents independently selected from halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, and halo(C1-C6)alkoxy;
R3a is hydrogen, or (C1-C3)alkyl that is substituted with 0 or 1 substituent that is hydroxy, or (C1-C3)alkoxy;
R3b is hydrogen, or (C1-C3)alkyl, provided that R3a and R3b are not both H when R4 is (R4-i);
R4 is (R4-i) or (R4-ii):

OG Complex Work Unit Chemistry
wherein:
R4N is (C1-C6)alkyl, halo(C1-C6)alkyl, or (C3-C6)cycloalkyl, wherein said (C1-C6)alkyl is substituted with 0 or 1 substituent that is hydroxy;
R4C is hydrogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, or (C3-C6)cycloalkyl, wherein said (C1-C6)alkyl and halo(C1-C6)alkyl are substituted with 0 or 1 substituent that is hydroxy, cyano, or (C1-C6)alkoxy;
R4D is hydrogen, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, or (C3-C6)cycloalkyl, wherein said (C1-C6)alkyl and halo(C1-C6)alkyl are substituted with 0 or 1 substituent that is hydroxy, cyano, or (C1-C6)alkoxy;
R4E is hydrogen, halogen, cyano, hydroxy, or (C1-C6)alkyl; and
R4F is hydrogen, halogen, cyano, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, or (C3-C6)cycloalkyl, wherein said (C1-C6)alkyl and halo(C1-C6)alkyl are substituted with 0 or 1 substituent that is hydroxy, cyano, or (C1-C6)alkoxy.